In the Americas, bats represent a major reservoir for rabies virus (RV) and most of the human rabies cases that were reported during the last twenty years in the US were caused by RV variants that circulate in bat species. Unlike the classical human rabies transmission by rabid terrestrial carnivores, most of theses human rabies cases occurred without evidence of exposure to the virus by way of recognized bites or scratches. However, RV in bats is not well studied. Based on our preliminary results, our overall hypothesis for this study is: There are significant differences in regard to mode of virus transmission, viral spread, and virus shedding in bats infected with either the bat rabies variant causing most human rabies cases in the US, another bat rabies variants, or a rabies virus variant causing rabies cycles in terrestrial carnivores. Aim 1: Compare the pathogenicity of bat-associated and classical RV strains in a bat animal model. Aim 2. Study the mode of transmission, spread and immunogenicity of bat-derived SHBRV in the big brown bat animal model. The results should reveal possible routes of virus transmission within bat colonies as well as unique attributes of RV pathogenicity in bats, and therefore support the concept that bats represent a unique reservoir of RV that plays a significant role in the infection of other mammals including humans. Therefore, this study should contribute to an understanding of how bats in general can serve as reservoirs for emerging infectious diseases. PUBLIC HEALTH RELEVANCE: Rabies virus is a devastating neuronal disease, which affects animal and humans. Bats might serve as a reservoir for rabies with important implications for human health